Cardiovascular and locomotor effects of binary mixtures of common 'bath salts' constituents: Studies with methylone, methylenedioxypyrovalerone and caffeine in rats.

Background And Purpose: The use of 'bath salts' drug preparations has been associated with high rates of toxicity and death. Preparations often contain mixtures of drugs, including multiple synthetic cathinones or synthetic cathinones and caffeine. Little is known about the interactions of 'bath salts' constituents and adverse effects often reported by users.

Exceeding the limits of paediatric heat stress tolerance: the risk of losing a generation to climate inaction.

Greenhouse gas (GHG) emissions are creating unprecedented climate-driven extreme weather, with levels of heat and humidity surpassing human physiological tolerance for heat stress. These conditions create a risk of mass casualties, with some populations particularly vulnerable due to physiological, behavioural and socioeconomic conditions (eg, lack of adequate shelter, limited healthcare infrastructure, sparse air conditioning access and electrical grid vulnerabilities). Children, especially young children, are uniquely vulnerable to extreme heat-related morbidity and mortality due to factors including low body mass, high metabolism, suboptimal thermoregulatory mechanisms and behavioural vulnerabilities.

Item-Level Analysis of Category Fluency Test Performance: A Systematic Review and Meta-Analysis of Studies of Normal and Neurologically Abnormal Ageing.

While Category Fluency (CF) is widely used to help profile semantic memory, item-level scoring (ILS) approaches to this test have been proposed to obtain indices that are less influenced by non-semantic supportive functions. We systematically reviewed the literature to test the hypotheses that (1) compared with healthy adults, individuals with a clinical diagnosis suggestive of neurodegeneration generate words of lower semantic complexity; (2) compared with young adults, older adults generate words of higher semantic complexity. We searched six databases (date of search: 8 December 2023) for studies that relied on CF and ILS methods, in normal ageing and in age-associated neurodegeneration.

Healthy Aging and the Gut Microbiome in People With and Without HIV.

Background: Aging-related comorbidities are more common in people with human immunodeficiency virus (HIV) compared to people without HIV. The gut microbiome may play a role in healthy aging; however, this relationship remains unexplored in the context of HIV.

Methods: 16S rRNA gene sequencing was conducted on stool from 1409 women (69% with HIV; 2304 samples) and 990 men (54% with HIV; 1008 samples) in the MACS/WIHS Combined Cohort Study.

Human Endogenous Retrovirus K in Astrocytes Is Altered in Parkinson's Disease.

Background: Parkinson's disease (PD) is the most common neurodegenerative movement disease. Human endogenous retroviruses (HERVs) are proviral remnants of ancient retroviral infection of germ cells that now constitute about 8% of the human genome. Under certain disease conditions, HERV genes are activated and partake in the disease process.

Cripto-1 acts as a molecular bridge linking nodal to ALK4 via distinct structural domains.

The TGF-β family ligand Nodal is an essential regulator of embryonic development, orchestrating key processes such as germ layer specification and body axis formation through activation of SMAD2/3-mediated signaling. Significantly, this activation requires the co-receptor Cripto-1. However, despite their essential roles in embryogenesis, the molecular mechanism through which Cripto-1 enables Nodal to activate the SMAD2/3 pathway has remained elusive.

Chemical and temporal manipulation of early steps in protein assembly tunes the structure and intermolecular interactions of protein-based materials.

The Drosophila intrinsically disordered protein Ultrabithorax (Ubx) undergoes a series of phase transitions, beginning with noncovalent interactions between apparently randomly organized monomers, and evolving over time to form increasingly ordered coacervates. This assembly process ends when specific dityrosine covalent bonds lock the monomers in place, forming macroscale materials. Inspired by this hierarchical, multistep assembly process, we analyzed the impact of protein concentration, assembly time, and subphase composition on the early, noncovalent stages of Ubx assembly, which are extremely sensitive to their environment.

Clinical and surgical factors influencing screw breakage during hardware removal following periacetabular osteotomy.

Periacetabular osteotomy (PAO) is a procedure used to treat patients with hip dysplasia. Current literature reports symptomatic hardware removal (HWR) rates of 13.6% following PAO.

Genotype-function-phenotype correlations for SCN1A variants identified by clinical genetic testing.

Objective: Interpretation of clinical genetic testing, which identifies a potential genetic etiology in 25% of children with epilepsy, is limited by variants of uncertain significance. Understanding functional consequences of variants can help distinguish pathogenic from benign alleles. We combined automated patch clamp recording with neurophysiological simulations to discern genotype-function-phenotype correlations in a real-world cohort of children with SCN1A-associated epilepsy.

Extracellular cold-inducible RNA-binding protein in CNS injury: molecular insights and therapeutic approaches.

Central nervous system (CNS) injuries, such as ischemic stroke (IS), intracerebral hemorrhage (ICH) and traumatic brain injury (TBI), are a significant global burden. The complex pathophysiology of CNS injury is comprised of primary and secondary injury. Inflammatory secondary injury is incited by damage-associated molecular patterns (DAMPs) which signal a variety of resident CNS cells and infiltrating immune cells.

OGG1 and MUTYH repair activities promote telomeric 8-oxoguanine induced senescence in human fibroblasts.

Telomeres are hypersensitive to the formation of the common oxidative lesion 8-oxoguanine (8oxoG), which impacts telomere stability and function. OGG1 and MUTYH glycosylases initiate base excision repair (BER) to remove 8oxoG or prevent mutation. Here, we show OGG1 loss or inhibition, or MUTYH loss, partially rescues telomeric 8oxoG-induced premature senescence and associated proinflammatory responses, while loss of both glycosylases causes a near complete rescue in human fibroblasts.

Retrospective Evaluation of Novel Synthetic Opioids and Xylazine Chronic Intake by Post-Mortem Hair Testing.

Fentanyl and its derivatives (nonpharmaceutical fentanyl, NPFs) represent the largest group among synthetic opioids. Fentanyl-related deaths and fatalities from tampering with pharmaceutical products have been reported. Furthermore, in the United States, adulterants such as xylazine and other substances, including the nitazenes class of opioids, have been found in an increasing number of unintentional overdose deaths, drug seizures, and reports of use by recreational drug users.

Healthcare Contact Days Pre- and Post-Liver Transplant in Patients with Cirrhosis: A National Cohort Study.

Introduction: "Healthcare contact days" is a patient-centered quantitative proxy for time toxicity, which can be informative for liver transplant (LT) decision-making. We aimed to (i) quantify contact days in patients with cirrhosis pre- and post-LT; (ii) identify clinical and demographic features associated with contact days.

Methods: Using a national health system database, we calculated healthcare contact days (inpatient, outpatient hospital [e.

Machine Learning-Based Prediction of Binge Drinking among Adults in the United State: Analysis of the 2022 Health Information National Trends Survey.

Little is known about the association of social media and belief in alcohol and cancer with binge drinking. This study aimed to perform feature selection and develop machine learning (ML) tools to predict occurrence of binge drinking among adults in the United State. A total of 5,886 adults including 1,252 who ever experienced with binge drinking were selected from the 2022 Health Information National Trends Survey (HINTS 6).

How Polyproline Type II Conformation at P Residues Influences the Success of Proline-Based Peptidyl Inhibitors Against Coronavirus Main Protease.

In the wake of the pandemic, peptidyl protease inhibitors with Pro-based rigid Leu mimetics at the P position have emerged as potent drug candidates against the SARS-CoV-2 main protease. This success is intuitively attributed to the enhanced hydrophobic interactions and rigidity of Pro-based rigid Leu mimetics in the literature. However, the tertiary amide of proline P derivatives, which hinders the formation of a critical hydrogen bond with the enzyme active site, and the constrained PP conformation, which contradicts the protease preferred β-strand conformation, represent two overlooked disadvantages associated with these inhibitors over traditional inhibitors and, theoretically, should adversely affect their potency.

A phase II study of ramucirumab and somatostatin analog therapy in patients with advanced neuroendocrine tumors.

Objectives: Well-differentiated neuroendocrine tumors (NET) are highly vascular tumors characterized by their expression of vascular endothelial growth factor (VEGF). This trial investigated the activity of ramucirumab, a monoclonal antibody that targets VEGF receptor-2 (VEGFR-2) and inhibits activity of VEGF, in combination with somatostatin analog therapy in patients (pts) with advanced extra-pancreatic NET.

Methods: We conducted a single-arm phase II trial enrolling pts with advanced, progressive extra-pancreatic NET.

What Matters Most for Long-Acting Antiretroviral Therapy? A Best-Worst Scaling Discrete Choice Experiment.

Introduction: Florida remains a high-incidence, high-prevalence setting for HIV. Long-acting (LA) antiretroviral therapies (ART) could improve HIV-related outcomes and reduce transmission. This study identifies preferred LA ART characteristics and classes of preference among people with HIV (PWH) in Florida.

Genetic context modulates aging and degeneration in the murine retina.

Background: Age is the principal risk factor for neurodegeneration in both the retina and brain. The retina and brain share many biological properties; thus, insights into retinal aging and degeneration may shed light onto similar processes in the brain. Genetic makeup strongly influences susceptibility to age-related retinal disease.

A first-in-human study of JNJ-70218902, a bispecific T-cell-redirecting antibody against TMEFF2 in metastatic castration-resistant prostate cancer.

Background: Metastatic castration-resistant prostate cancer (mCRPC) has a poor prognosis, necessitating the investigation of novel treatments and targets. This study evaluated JNJ-70218902 (JNJ-902), a T-cell redirector targeting transmembrane protein with epidermal growth factor-like and 2 follistatin-like domains 2 (TMEFF2) and cluster of differentiation 3, in mCRPC.

Patients And Methods: Patients who had measurable/evaluable mCRPC after at least one novel androgen receptor-targeted therapy or chemotherapy were eligible.

Assessing Links Between Alcohol Exposure and Firearm Violence: A Scoping Review Update.

Background: Firearm violence remains a leading cause of death and injury in the United States. Prior research supports that alcohol exposures, including individual-level alcohol use and alcohol control policies, are modifiable risk factors for firearm violence, yet additional research is needed to support prevention efforts.

Objectives: This scoping review aims to update a prior 2016 systematic review on the links between alcohol exposure and firearm violence to examine whether current studies indicate causal links between alcohol use, alcohol interventions, and firearm violence-related outcomes.

Differential Effects of Alcohol Policies Across Race/Ethnicity and Socioeconomic Status.

Purpose: Sociocultural characteristics, including race/ethnicity and socioeconomic status (SES), may affect individuals' attitudes and norms regarding alcohol use and treatment as well as their access to emerging health knowledge, innovative technologies, and general resources for improving health. As a result of these differences, as well as social determinants of health such as stigma and uneven enforcement, alcohol policies may not benefit all population subgroups equally. This review addresses research conducted within the last decade that examined differential effects of alcohol policies on alcohol consumption, alcohol harm, and alcohol treatment admissions across racial/ethnic and socioeconomic groups.

Do delayed responses introduce bias in ecological momentary assessment? Evidence from comparisons between self-reported and objective physical activity.

Introduction: Delayed responses are a common yet often overlooked aspect of participant compliance in ecological momentary assessment (EMA) research. This study investigated whether response delays introduce selection bias in the moments captured by EMA.

Methods: Participants ( = 339) self-reported their physical activity behaviors using EMA five times a day over 7 days while wearing a continuous physical activity monitor.

Associations Among Emotion Regulation, COVID Stress, Alcohol Use, and Intimate Partner Aggression Among College Students During the COVID-19 Pandemic.

Purpose: Intimate partner aggression (IPA) increased after the onset of the COVID-19 pandemic. Following the Vulnerability-Stress-Adaptation (VSA) model, the current study examined associations among emotion regulation (ER) difficulties (an enduring vulnerability), COVID stress (a current stressor), alcohol use (a maladaptive coping strategy), and physical, psychological, and cyber IPA perpetration during the first eight months of the pandemic.

Method: Participants were 215 college students in current relationships from three universities across the US.

Maturation of striatal dopamine supports the development of habitual behavior through adolescence.

Developmental trajectories during the transition from adolescence to adulthood contribute to the establishment of stable, adult forms of operation. Understanding the neural mechanisms underlying this transition is crucial for identifying variability in normal development and the onset of psychiatric disorders, which typically emerge during this time. Habitual behaviors can serve as a model for understanding brain mechanisms underlying the stabilization of adult behavior, while also conferring risk for psychopathologies.

Preliminary effects of oral ANS-6637, an ALDH2 inhibitor, on cue-induced craving, safety and alcohol consumption among adults with alcohol use disorder: a proof-of-concept, randomized, human laboratory trial.

Aims: We evaluated the safety, efficacy, and patient adherence to oral ANS-6637, a selective, reversible inhibitor of aldehyde dehydrogenase 2 (ALDH2), for treating alcohol use disorder (AUD).

Methods: A 3-arm, double-blind, randomized, proof-of-concept human laboratory study embedded in a 5-week multisite clinical trial tested 200 mg and 600 mg daily doses of ANS-6637 compared to placebo in treatment-seeking adults with AUD. After 1 week of medication, participants completed an alcohol cue reactivity session.